This proposal represents a novel, integrative approach to the study of hormone-mediated and memory-induced morphological change in the avian hippocampus. In large part, birth of cortical neurons occurs only in the young developing brain and not in adulthood such that the brain is thought to be in a constant state of age-related degeneration and neuron loss. This does not appear to be the case in the hippocampus of adult birds and mammals which retains the capacity for substantial plasticity including the genesis of new neurons in response to (1) enriched environments, (2) changes in season, (3) performing specific behaviors such as storing and retrieving food, and (4) performing spatial learning tasks. The ability of the brain to respond to environmental influences, both internal (e.g., hormones) and external (e.g., learning experiences), through the process of neurogenesis has exciting scientific potential and profound implications for mental health. A recent intriguing finding is that new hippocampal cells are born as a result of damage. Since the hippocampus has retained the ability to recruit new neurons, we can use this result to investigate those factors influencing cytogenesis and differentiation of these new cells into neurons and glia. Using this model, we have the potential to start unraveling some of the factors mediating hippocampal plasticity especially neurogenesis. Our aim is to exploit the ability of the avian hippocampus to respond to environmental influences by investigating ways in which memory formation and hormones influence neural proliferation, migration, and differentiation by asking 3 basic questions: (1) Where and when are new hippocampal cells born and how long do they take to reach their destination?; (2) Does memory formation on a spatial learning task alter patterns of neuron or glia proliferation, migration, or differentiation and do estrogens change these patterns?; and (3) Is the damaged hippocampus capable of showing prolonged effects of neurogenesis resulting in recovery of function and can estrogens aid in this repair and recovery? A strong, integrative approach will be taken that exploits Dr. Lee's skills in avian neurobiology of learning and memory, and Dr. Schlinger's expertise in avian neurobiology and neuroendocrinology specifically hormone-mediated changes in behavior and neural growth. Zebra finches will be trained on a spatial learning task known to depend upon an intact hippocampus. Birds will be given lesions and the impact of these lesions on behavior as well as brain plasticity will be investigated. Effects of ovariectomy and estrogen-replacement will also be determined by (1) training ovariectomized females, both estrogen-replaced and non- replaced, on the spatial learning task, (2) lesioning the hippocampus, then (3) re-training the birds over a long period of time to determine how estrogens and behavior influence plastic changes and recovery of function in the hippocampus.